Consumption of antimicrobial manuka honey does not significantly perturb the microbiota in the hind gut of mice

The aim of this study was to test the hypothesis that consuming manuka honey, which contains antimicrobial methylglyoxal, may affect the gut microbiota. We undertook a mouse feeding study to investigate whether dietary manuka honey supplementation altered microbial numbers and their production of organic acid products from carbohydrate fermentation, which are markers of gut microbiota function. The caecum of C57BL/6 mice fed a diet supplemented with antimicrobial UMF® 20+ manuka honey at 2.2 g/kg animal did not show any significantly changed concentrations of microbial short chain fatty acids as measured by gas chromatography, except for increased formate and lowered succinate organic acid concentrations, compared to mice fed a control diet. There was no change in succinate-producing Bacteroidetes numbers, or honey-utilising Bifidobacteria, nor any other microbes measured by real time quantitative PCR. These results suggest that, despite the antimicrobial activity of the original honey, consumption of manuka honey only mildly affects substrate metabolism by the gut microbiota

Current Landscape of Immunotherapy for the Treatment of Metastatic Non-Small-Cell Lung Cancer

For patients with advanced non-small-cell lung cancer (NSCLC) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents—atezolizumab, nivolumab, and pembrolizumab—have been shown to be superior to chemotherapy in the second-line setting. For patients with tumours strongly expressing PD-L1, pembrolizumab has been associated with improved outcomes in the first-line setting. Demonstration of the significant benefits of immunotherapy in NSCLC has focused attention on new questions. Combination checkpoint regimens, with acceptable toxicity and potentially enhanced efficacy, have been developed, as have combinations of immunotherapy with chemotherapy. In this review, we focus on the published trials that have changed the treatment landscape in advanced NSCLC and on the ongoing clinical trials that offer hope to further improve outcomes for patients with advanced NSCLC

Immunotherapy targeting inhibitory Fc? receptor IIB (CD32b) in the mouse is limited by monoclonal antibody consumption and receptor internalization

Genetic deficiency of the inhibitory Fc receptor, Fc?RIIB (CD32b), has been shown to augment the activity of activatory Fc?R and promote mAb immunotherapy. To investigate whether mAbs capable of blocking Fc?RIIB have similar capacity, we recently generated a panel of specific anti-mouse Fc?RIIB mAbs that do not cross-react with other FcRs, allowing us to study the potential of Fc?RIIB as a therapeutic target. Previous work revealed a number of these mAbs capable of eliciting programmed cell death of targets, and in the present study we demonstrated their ability to promote target cell phagocytosis. However, in a variety of murine tumor models, anti-Fc?RIIB mAbs demonstrated limited therapeutic activity despite optimized treatment regimens. Unexpectedly, we observed that the anti-Fc?RIIB mAbs are rapidly and extensively consumed in vivo, both by the tumor and host cells, including B cells, leading to a precipitous loss from the circulation. Closer analysis revealed that the anti-Fc?RIIB mAbs become extensively internalized from the cell surface within 24 h in vivo, likely explaining their suboptimal efficacy. Subsequent studies revealed that anti-Fc?RIIB mAb immunotherapy was effective when used against Fc?RIIB+ tumors in Fc?RIIB?/? recipients, indicating that consumption of the mAb by nontumor cells is the primary limitation of these reagents. Importantly, similar rates of internalization were not seen on human target cells, at least in vitro. These studies further highlight the need to determine the propensity of mAb therapeutics to internalize target receptors and also identify potential key differences between human and mouse cells in this respect